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Male Biological clock

Dr. Sheena Lewis People often mistakenly assume they will be able to have children later in life

Tuesday, July 15, 2008
Timing is key to fathering children
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THERESA JUDGE
New research suggests men's biological clocks are also ticking
FERTILITY EXPERTS have warned there is a growing body of evidence showing that the man's age is a significant factor affecting the chances of a couple conceiving and of having a healthy child.
A new study presented last week at the annual meeting of the European Society of Human Reproduction and Embryology in Barcelona found that miscarriage rates increased significantly when the man was older than 35, and that pregnancy rates dropped when the man was older than 40. The study was based on more than 12,000 couples attending a fertility clinic in Paris.
Professor of reproductive medicine at Queen's University Belfast, Sheena Lewis, who also presented a paper at the conference, said the Paris study "provided more data to add to an emerging picture" relating to the significance of the age of the father.
She said people needed to realise that they are taking a risk by waiting until they were 35 years or older to have children - as an increasing number of women and men are. "You cannot assume that it will happen, that it will not be a problem," she said.
Prof Lewis, who is a scientist at the Regional Fertility Centre at the Royal Victoria Hospital in Belfast, said there was a growing trend of people leaving it later to have children when their careers were established, and of people trying to start second families later in life. She said the clinic was seeing an increasing number of men in their 40s and 50s who wanted to have children, often in a second relationship.
People often mistakenly assume they will be able to have children later in life, she said. "What happens is that we are inclined to take anecdotal evidence and assume that it applies to the whole population - so people hear about Cherie Blair and Madonna having babies and assume that older mothers can have easy pregnancies.
"And they hear about Picasso fathering a child when he was 81, and they believe that every man can do it, and it becomes the accepted wisdom, but unfortunately it is not the case. We are perpetuating a myth and people often believe it until it is too late," Prof Lewis said.
She said there were now quite a number of studies showing that as a man ages, the likelihood of his sperm being damaged increases. "A sperm is a very specialised little cell - it is just DNA with a tail and it has one single function, to get the DNA to the egg to fertilise it. In order to do that, the cell gets rid of everything but DNA, so it gets rid of repair mechanisms that you find in other cells. So if it gets damaged it can't repair itself."
She said that after fertilisation, the DNA damage of the sperm becomes part of the genetic make-up of the embryo. "If a poor sperm fertilises an egg, and even if you get a pregnancy, there is quite often a miscarriage," Prof Lewis said. While one study had suggested that an egg could repair a damaged sperm, she said there was not a great deal of evidence to support this, and further research would be needed to test it. She said other studies had shown that when a man is older it takes longer for a couple to conceive.
Dr Stephanie Belloc, who led the study at the Eylau Centre for Assisted Reproduction in Paris, told the Barcelona conference: "Until now gynaecologists only focused on maternal age and the message was to get pregnant before the age of 35 or 38, because afterwards it would be difficult. But now gynaecologists must also focus on paternal age and give this information to the couple."
The study examined 12,236 couples who had decided to try intra-uterine insemination (IUI) after having difficulty conceiving. This procedure involves spinning sperm in a centrifuge to separate it from seminal fluid and then inserting it directly into the womb.
Pregnancy, miscarriage and delivery rates were recorded as were the quality, activity and shape of the men's sperm. The analysis separated out male and female factors.
As expected, women over the age of 35 were less likely to get pregnant but the man's age was also found to be a significant factor both in miscarriage rates and pregnancy rates.
For men aged 34, the miscarriage rate was 16.7 per cent, but for men aged between 35 and 39 it rose to 19.5 per cent, and by age 44 it had reached 32.4 per cent.
Pregnancy rates only began to change significantly when the men reached the age of 40. As the men's age rose from 39 to 44 the proportion of treatment cycles producing a pregnancy fell from 13.4 per cent to 10.9 per cent.
Dr Belloc said the study "proves for the first time that there is a strong paternal age-related effect on IUI outcomes" and she said the findings were relevant to all couples wishing to have children.
Prof Lewis and her colleagues in Belfast are currently conducting research into "lifestyle hazards" that affect male fertility. These include smoking, alcohol, sexually transmitted diseases, recreational drugs and substances that mimic oestrogens which are found in some products ranging from certain foods, aerosols and body creams, and plastic food coverings. Much of the research in this area was prompted by a Danish finding in 1992 that men's sperm count had declined by 50 per cent in 50 years.
Prof Lewis said a recent study in Denmark had also found that 40 per cent of young men had a low sperm count. "It appears to be a particular problem in northern Europe," she said.
The paper she presented at last week's Barcelona conference concerned the impact of cannabis use on male fertility. The study found that cannabis use decreased sperm motility - the pace at which sperm can swim. Other studies have also shown that cannabis use reduces sperm production.
She said that men who wanted to become fathers should be aware that it takes about 70 days for a sperm to be produced, so the "lifestyle hazards" such as smoking and recreational drugs should be avoided for at least three months if they want their sperm to be healthy.
She also pointed out that studies suggest that a father smoking, and the resulting damage to the sperm DNA, can lead to an increase in certain childhood illnesses, in particular some forms of cancer and more recently an association has been found with autism.
"When a mother smokes and damages the egg, the egg has the capacity to repair the damage, but the damage to the sperm becomes part of the embryo's genetic make-up," she said.
© 2008 The Irish Times
This article appears in the print edition of the Irish Times

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Professor Sheena E.M. Lewis, BSc PhD
School of MedicineObstetrics and GynaecologyQueen’s University BelfastInstitute of Clinical ScienceGrosvenor RoadBelfast BT12 6BJN Ireland
e: s.e.lewis@qub.ac.uk
t: +44-28-9063-3987
f: +44-28-9032-8247
I am Professor and Director of the Reproductive Medicine research group here in Queen's having previously been Reader in Obstetrics and Gynaecology at Queen's University since October 2000. I was also appointed as an Honorary Consultant in the Royal Group of Hospitals in Belfast in 2003.Services to the scientific communityNationally, I am a regular reviewer for 10 specialist journals and for research charities including The Wellcome Trust, Wellbeing, and BBSRC.I am a member of the Practice and Policy committee of the British Fertility Society and on the Research and Development Fellowship Committee and Northern Ireland Forum for Health and Social Care Research for Northern Ireland.RESEARCH PUBLICATIONS62 peer reviewed publications, 9 review articles, 6 invited chaptersincluding 23 since 2000 (First or final author on 20)RESEARCH GRANTS AWARDED£1,000,000 including three from The Wellcome Trust.PROFESSIONAL SOCIETIES• British Fertility Society• British Andrology Society• Society for the Study of Fertility• International Society of Andrology• Institute of Learning and Teaching in Higher Education• Research and Development Fellowship Committee, N.I• Ulster Obstetrical and Gynaecological Society• Vice Chairperson of the Ladies Committee, Royal Maternity Hospital• Association of University TeachersINVITED GUEST SPEAKER AT RECENT SCIENTIFIC CONFERENCES• First Mediterranean Congress of Reproductive Medicine, Taormina, Sicily• Opening Doors-scientific workshop organised by British and Spanish Councils, Spain,• GSRMC (Good Samaritan Regional Medical Centre Phoenix, Arizona, USA)• UKEMS (The United Kingdom Environmental Mutagen Society)• British Fertility Society• British Andrology Society• Biology of Spermatozoa Annual Meeting• Senior Staff Conference, Royal College of Obstetrics and Gynaecologists• Association of Clinical Biochemists in IrelandINVITED SPEAKER BY MEDIA• BBC Radios 1, 2, 4 and 5• BBC News• Sky news• Ulster Television; UTV LIFE – CHAPS UK Study• Radio Eireann – Donor Sperm• Radio Ulster – Comment on Health Minister’s proposal and comment on BFS in Belfast.• British Satellite News - for CNN news, Tokyo News, Mid Eastern broadcasting and others• Ulster Television The Family Show- Infertility and LifestyleCENTRAL UNIVERSITY ACTIVITIES• Member of Academic Council of Queens University, Belfast• Mentor and mentee in Gender Initiative in Queen’s University, BelfastRESEARCH INTERESTSOur research interest is in Andrology; the study of male reproductive function. Our twin aims are:i) to understand the endocrine, cellular and molecular reproductive dysfunctions in infertile men compared with a fertile baseline. Within this framework, we have focused on specific lifestyle, environmental and disease factors that may exacerbate infertilityii) to establish novel prognostic tests to enhance assisted conceptionOngoing projects:Lifestyle hazards: recreational drugsi) to determine the in vivo and in vitro effects of tetrahydrocannabinoid; THC the primary psychoactive cannabinoid in marijuana on human sperm functionii)the effects of Viagra on sperm function and early embryo development using human and animal modelsEnvironmental hazardsthe effects of dietary phytoestrogens on male reproductive healthDiseases exacerbating male infertilityEndocrine, cellular and molecular effects of diabetes and impotence treatments (first generation Viagra and second generation Tadalafil) on male fertilityDevelopment of novel male fertility tests with prognostic value in assisted conception• assessment of sperm nuclear and mitochondrial DNA iv)investigation of the failure of post-vasectomy testicular sperm to achieve pregnancies by ICSI• the regulation of spermatogenesis by apoptosis in fertile men and males with obstructive azoospermia- clinical implications• Ubiquitin tagging ( internal and surface) on sperm and its implications for male fertility (in collaboration with Dr Peter Sutovsky, Columbia-Missouri )Future Studies• Genetic and epigenetic alterations associated with spontaneous abortion achieved by assisted conception (in collaboration with Dr Ken McIlreavey, Pasteur Institute, Paris and Dr Colum Walsh, University of Ulster )
Obstetrics and Gynaecology at Queen's.

Among couples with fertility problems, those in which the man is over age 35 have lower pregnancy rates and increased chances of miscarriage,

Father's Age a Factor in Infertility

MONDAY, July 7 (HealthDay News) -- Among couples with fertility problems, those in which the man is over age 35 have lower pregnancy rates and increased chances of miscarriage, a new study shows.
To come to this conclusion, French researchers looked at more than 12,000 couples who went to a fertility clinic in France.

In most of the cases, the couples were being treated due to the man's infertility. The couples underwent a total of 21,239 intrauterine inseminations (IUIs).

The researchers found that women over age 35 had a pregnancy rate of 8.9 percent, compared to 14.5 percent in younger women.

"But we also found that the age of the father was important in pregnancy rates -- men over 35 had a negative effect. And, perhaps more surprisingly, miscarriage rates increased where the father was over 35," study author Dr. Stephanie Belloc, of the Eylau Center for Assisted Reproduction in Paris, said in a prepared statement.

The female biological clock—its tick-tock marking the decline of fertility that grows louder as a woman reaches middle age—is deeply ingrained in popular consciousness. Take this scene from the film Bridget Jones's Diary: Bridget's Uncle Geoffrey reminds her that as a career girl she "can't put it off forever," alluding to her declining fertility. His wife Una chimes in: "tick-tock, tick-tock," her finger wagging like a metronome.
The biological clock, although just a metaphor, refers to a real phenomenon: Women over 35 years of age are only half as likely to become pregnant in the most fertile part of their menstrual cycle than women younger than 26.

So do men suffer from the same thing?

"For women, a biological clock is a decline in fertility and an increased chance of having genetically abnormal babies as they age," says Harry Fisch, director of New York City's Male Reproductive Center and author of The Male Biological Clock: The Startling News About Aging, Sexuality, and Fertility in Men. "And that's exactly what's happening with men."

So how did Indian farmer Nanu Ram Jogi sire a healthy child at the age of 90 last year? Such a feat would be impossible for a woman, even in an age when Carmela Bousada, 67, gave birth to twins in January 2007 after lying about her age to the doctors who gave her in vitro fertilization. Whereas fertility declines along with testosterone levels as men age, it doesn't drop to zero.

Still, Jogi is definitely the exception rather than the rule. One study found that the odds of fatherhood for those under the age of 30 was 32.1 percent compared with 20 percent over the age of 50, signifying a 38 percent drop in male fertility across that age gap.

One study examined 97 men between the ages of 22 and 80 and found that as they aged their semen volume decreased by 0.001 ounce (0.03 milliliter) per year from an average total of 0.09 ounce (2.7 milliliters) and their "total progressively motile sperm count"—a rough index for the fertility potential of one's sperm based on its movement—decreased about five percent with each year they aged.

Fisch and his colleagues have also found that the children of women over 35 whose babies' fathers were also of that age were more likely to have Down's syndrome than offspring whose fathers were younger.

In other studies, older men were more likely to father children with mental illness or other deficits. Roughly 11 children out of a thousand conceived by men over age 50 developed schizophrenia compared with under three children out of a thousand for fathers under 20 in one study from the Archives of General Psychiatry. And the children of men 40 years or older were nearly six times more likely to have autism spectrum disorders than kids begot by men under 30.

So do men's sperm get staler over time? To maintain sperm levels, cells known as germ cells must continue dividing. After all, men find ways to dispose of sperm—ahem—and once ejaculated they only survive for several days. By the age of 50, these germ cells will have divided 840 times. Each one of those divisions is an opportunity for something to go wrong. "There's more of a chance to have genetic abnormalities the more the cells divide," Fisch says. In sperm these mutations dot the genes with changes in the basic structure of the DNA—and can lead to problems in the resulting offspring.


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Men's fertility decreases after 35, study confirms

Men's fertility decreases after 35, study confirms
Email Printer friendly version Normal font Large font Kate Benson Medical Reporter
July 7, 2008
IT HAS long been known that a woman's chance of reproducing declines once she hits 35, but now scientists have found that men who have some forms of fertility treatment in their 30s suffer the same fate.

A study by Laboratoire d'Eylau, a centre for assisted reproduction in Paris, followed more than 21,000 men who had intrauterine inseminations at fertility clinics. It found the process, where semen is washed to extract the sperm, resulted in a decrease in pregnancies and an increase in miscarriages.

All the men in the study, which will be presented today at the annual conference of the European Society for Human Reproduction and Embryology, were aged over 35.

"We already believed that couples where the man was older took longer to conceive," said the study's author, Stephanie Belloc.

"But how DNA damage in older men translates into clinical practice has not been shown up to now. Our research shows for the first time that there is a strong paternal age-related affect on [intrauterine insemination] outcomes and this information should be considered by both doctors and patients in assisted reproduction."

She said sperm with DNA damage, common in older men, could still enter the egg during intrauterine insemination, which could result in a failure to conceive or a miscarriage.

But during in vitro fertilisation, the zona pellucida, or outer membrane of the egg, was an efficient barrier in preventing the penetration of sperm with DNA damage.

"And in ICSI [intracytoplasmic sperm injection], the best sperm can be selected for use. These methods, although not in themselves a guarantee of success, may help couples where the man is older to achieve a pregnancy more quickly and reduce the risk of miscarriage," Dr Belloc said.

She followed 21,239 patients, and examined the sperm of each partner for count, motility and morphology. Pregnancy rates, miscarriage and delivery rates were also recorded.

"Some recent studies have established a relationship between the results of [intrauterine insemination] and DNA damage, which also correlated to a man's age, suggesting it might be an important factor, but until now there was no clinical proof. We have now found that the age of the father was important in pregnancy - men over 35 had a negative effect."